Some of the most exciting recent research advances in human molecular genetics involve the isolation or impending isolation of human disease genes. Such successes provide improved diagnostic capabilities but, at the same time, introduce basic questions regarding the biologic function, regulation and expression of gene products, raising hopes of workable therapeutic modalities. The more important current problems revolve about strategies for more rapid cloning and expression systems and include classification of mouse-human homologies' relative to the development of appropriate animals models of human disease states leading to better gene therapy approaches. This multidisciplinary meeting will convene a group of outstanding investigators, all of whom are internationally recognized authorities in their respective fields of research. The past two years have witnessed significant progress in several areas of investigation with exciting implications for the management and possible treatment of genetic diseases. These advances will be discussed in sessions on: novel inheritance patterns; cancer etiologies; human disease "knockouts"/animal models; homologous recombination/mouse models; specific human disease genes/mutational analysis; human gene therapy; gene mapping and cloning; and human molecular cytogenetics. This meeting is being held in conjunction with a companion Keystone symposium devoted specifically to gene therapy. A previous format of this particular combination (1992) proved extremely successful and provides an interface for scientists working in basic and clinical research areas of animal and human genetics. Most of these investigators are NIH-supported and their participation in this symposium will be underwritten by the award of this application, not to be supplemented by funds from individual research grants. This symposium constitutes a unique forum for the presentation of newer approaches to clinically relevant issues in human inherited diseases.